Is the genetics of disease susceptibility and progression shared? 🤷♂️
We look at this question within a global biobank collaboration across 10 major diseases
We look at this question within a global biobank collaboration across 10 major diseases
Comments
Most drugs are developed to cure diseases, not to prevent them. Most of us see a doctor once we are already sick, so genetic prediction of disease progression is clinically relevant.
Our preprint 👉
https://www.medrxiv.org/content/10.1101/2023.10.10.23296544v1
We compared these results with results from GWAS of disease susceptibility (i.e. traditional case-control).
What did we find?
None of 888 susceptibility loci was significantly associated with disease mortality.
Despite this being the largest GWAS for most diseases, we found only 1 disease mortality locus
Using a downsampling experiment we show this is not the case.
Disease susceptibility PGS can't be used to predict disease mortality and vice versa.
Interestingly, we found genetics of general longevity sometimes predicts patients' survival better
Our results suggest heritability for disease-caused mortality can be just too low.
In this case, index event bias, a major concern for progression studies, becomes less concerning and does not solely explain our results